Objective: Our goal is to kill tumor cells selectively by treating tumor-bearing hosts with potent cytotoxins conjugated to tumor-specific antibodies. Approach: We have already shown that diphtheria toxin conjugated to antibodies against cell-surface antigens can kill selectively cells which bear those antigens. Such antibody-toxin conjugates exert antitumor effects in vivo when prepared with antibodies directed against tumor-specific antigens. To date, however, their therapeutic usefulness against experimental tumors has been limited by their content of toxic but immunologically non-specific impurities. We are trying to improve the therapeutic efficacy of this approach to the point where treatment with conjugates induces regressions of established tumors, using the following methods: 1. Improved purification of conjugates utilizing immunoadsorbent techniques. 2. Combined chemoimmunotherapy. 3. Utilization of chemically modified or of mutant diphtheria toxins known to have reduced binding affinity for cells, to minimize the non-specific toxicity of conjugates. 4. Preparation and evaluation of conjugates between antibodies and cytotoxic agents other than diphtheria toxin. These include ricin, phospholipase C, and pancreatic ribonuclease. Recent Progress: Recently, we have been able to show that antibodies against tumor antigens induced by SV40 virus, conjugated to diphtheria toxin, can effect permanent regressions of transplanted hamster lymphomas bearing SV40-induced cell-surface antigens.